19-54108354-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_013342.4(TFPT):c.395G>A(p.Arg132Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,610,476 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R132W) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
TFPT
NM_013342.4 missense
NM_013342.4 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 5.49
Genes affected
TFPT (HGNC:13630): (TCF3 fusion partner) Predicted to enable DNA binding activity and protein kinase binding activity. Involved in apoptotic signaling pathway. Located in nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]
NDUFA3 (HGNC:7686): (NADH:ubiquinone oxidoreductase subunit A3) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFPT | NM_013342.4 | c.395G>A | p.Arg132Gln | missense_variant | 4/6 | ENST00000391759.6 | |
TFPT | NM_001321792.2 | c.368G>A | p.Arg123Gln | missense_variant | 4/6 | ||
TFPT | XM_005278261.2 | c.35G>A | p.Arg12Gln | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFPT | ENST00000391759.6 | c.395G>A | p.Arg132Gln | missense_variant | 4/6 | 1 | NM_013342.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000450 AC: 11AN: 244456Hom.: 0 AF XY: 0.0000453 AC XY: 6AN XY: 132380
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GnomAD4 exome AF: 0.0000302 AC: 44AN: 1458356Hom.: 0 Cov.: 33 AF XY: 0.0000345 AC XY: 25AN XY: 725190
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2023 | The c.395G>A (p.R132Q) alteration is located in exon 4 (coding exon 4) of the TFPT gene. This alteration results from a G to A substitution at nucleotide position 395, causing the arginine (R) at amino acid position 132 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0722);.;Loss of MoRF binding (P = 0.0722);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at